BERMAD: batch effect removal for single-cell RNA-seq data using a multi-layer adaptation autoencoder with...

Removal of batch effect between multiple datasets from different experimental platforms has become an urgent problem, since single-cell RNA sequencing (scRNA-seq) techniques developed rapidly. Although there have been some methods for this problem, most of them still face the challenge of under-correction or over-correction. Specifically, handling batch effect in highly nonlinear scRNA-seq data requires a more powerful model to address under-correction. In the meantime, some previous methods focus too much on removing difference between batches, which may disturb the biological signal heterogeneity of datasets generated from different experiments, thereby leading to over-correction.

In this article, we propose a novel multi-layer adaptation autoencoder with dual-channel framework to address the under-correction and over-correction problems in batch effect removal, which is called BERMAD and can achieve better results of scRNA-seq data integration and joint analysis. First, we design a multi-layer adaptation architecture to model distribution difference between batches from different feature granularities. The distribution matching on various layers of autoencoder with different feature dimensions can result in more accurate batch correction outcome. Second, we propose a dual-channel framework, where the deep autoencoder processing each single dataset is independently trained. Hence, the heterogeneous information that is not shared between different batches can be retained more completely, which can alleviate over-correction. Comprehensive experiments on multiple scRNA-seq datasets demonstrate the effectiveness and superiority of our method over the state-of-the-art methods.

The code implemented in Python and the data used for experiments have been released on GitHub (https://github.com/zhanglabNKU/BERMAD) and Zenodo (https://zenodo.org/records/10695073) with detailed instructions.